LITHIUM-THERAPY IN THE TREATMENT OF MANIC-DEPRESSIVE ILLNESS - PRESENT STATUS AND FUTURE PERSPECTIVES - A CRITICAL-REVIEW

This article reviews critically the present status of lithium in the t reatment and prophylaxis of manic-depressive illness compared to the t wo anticonvulsant drugs, carbamazepine and valproic acid, Lithium is u sed successfully in the prophylaxis and treatment of manic-depression. The mechanism by which it exerts its effects is still not very clear. There is much evidence to indicate that lithium may exert its therape utic action by interfering with the metabolism of phosphoinositides wh ich play an important role in synaptic transmission. Because of lithiu m's narrow therapeutic/toxic ratio, blood concentration monitoring is crucial. Published data suggest that, compared to lithium, carbamazepi ne is similar in its relative specificity in treating mania, It is oft en faster in achieving its antimanic effects and best established as a n alternative for patients not responding or intolerant to lithium, Ca rbamazepine is a good substitute for lithium when severe renal problem s exclude the use of lithium. The therapeutic profile of valproic acid in manic-depression, although less extensively studied, appears to be similar to that of carbamazepine. As carbamazepine, it seems to be be st indicated in patients with rapid cycles. Whereas lithium inhibits m yo-inositol monophosphatase, carbamazepine shows a stimulating effect and valproic acid has no effect on this biochemical target. The implic ation of the inositol pathway in the pathogenesis of adverse effects, such as neurotoxicity and dermatological irritation, is discussed. A f urther understanding of this pathway is important for the future devel opment of new lithium-like compounds in order to maximize the therapeu tic benefits without the adverse effects.